The purpose of this study was to identify the adrenergic receptor type, either alpha or beta, responsible for mediating the previously observed potentiative actions of norepinephrine (NE) on inhibitory synaptic mechanisms in cerebellum and cerebral cortex. Inhibitory responses of rat somatosensory cortical and cerebellar Purkinje neurons to pulsatile iontophoretic administration of γ-aminobutyric acid (GABA) or activation of afferent synaptic pathways were examined before, during and after microiontophoresis of NE, isoproterenol or phenylephrine. Adrenergic agonist actions were quantitatively assessed by computer-based analysis of poststimulus time or GABA response histograms. At ejection currents which suppressed or had no effect on spontaneous discharge, the beta specific agonist, isoproterenol, augmented GABA-induced depressant actions in cerebellum (19 of 23 cells) and cerebral cortex (8 of 13 cells). The alpha agonist, phenylephrine, at similar dose was ineffective in enhancing neuronal responsiveness to GABA in either brain region (cerebellum n = 19; cortex, n = 19). Likewise, isoproterenol (12 of 12 cases) but not phenylephrine (n = 13) routinely facilitated inhibitory responses of somatosensory cortical neurons evoked by mechanical stimulation of the contralateral forepaw. Thus, only the beta agonist consistently mimicked the potentiative actions of NE on inhibitory processes in cerebellum and cerebral cortex. Furthermore, iontophoretic application of the beta blocking agent, sotalol, reversibly antagonized NE-mediated enhancement of GABA efficacy in six of eight Purkinje and three of four cerebrocortical cells, whereas the alpha antagonist, phentolamine, was ineffective in blocking noradrenergic facilitating actions in six of seven cerebellar neurons. These results suggest that release of endogenous NE from noradrenergic nerve terminals in cerebellum and cerebral cortex may augument inhibitory synaptic events by subsequent activation of beta adrenergic receptors.
|Original language||English (US)|
|Number of pages||12|
|Journal||Journal of Pharmacology and Experimental Therapeutics|
|State||Published - 1982|
All Science Journal Classification (ASJC) codes
- Molecular Medicine